He made his Major League debut on June 24, 2001 against the Cincinnati Reds, pitching six innings and allowing five earned runs. He recorded his first credited win on July 2 in a seven-inning start against the Milwaukee Brewers. He appeared in 13 games, with 9 starts in 2001, finishing 3-1 with a 5.50 ERA. He split 2002 between the AAA New Orleans Zephyrs and the Astros, before becoming a regular part of the Houston rotation in 2003. He made 32 starts that year, finishing 10-14 with a 3.68 ERA. In 2004, he was in 27 games, but only 17 were starts and he was 5-7 with a 5.72 ERA.

In 2005, Redding would go 0-5 with a 9.31 ERA in nine games (6 starts) with the Padres, while battling injuries, until he was traded to the New York Yankees with Darrell May for Paul Quantrill. The Yankees starting rotation was hurt by injuries and they decided to take "a chance" with Redding.[3] However, his stint with the Yankees would be short lived—he started and lasted one inning against the Boston Red Sox, allowing six runs on four hits and four walks. The next day, he was designated for assignment to allow a spot for pitcher Al Leiter. He spent the rest of the season in AAA with the Columbus Clippers.

In 2006, Redding spent the entire season in the minor leagues.[4] He signed a minor league contract with the Chicago White Sox and was assigned to their Triple-A affiliate, the Charlotte Knights. He became a key component of the Knights' pitching rotation, finishing the 2006 season with a 12-10 record and 3.40 ERA in 29 appearances. He led the team in strikeouts (148) and complete games (5). On September 6, 2006, Redding pitched a four-hit shutout against the Toledo Mudhens in the International League playoffs. At the end of the season, he opted for minor league free agency, and in November signed a minor-league deal with the Washington Nationals.

In 2007, with the Nationals, Redding had a rough spring training, allowing 11 runs in 8-2/3 inning, and not making the major league club. At Triple-A Columbus, he compiled a 9-5 record with an ERA of 5.32, by the end of June. The Nationals, beset by injuries to its starting pitching rotation, purchased Redding's contract, and in July he made his first big league start since 2005. He went 5 innings, being tagged with three runs and the loss. He followed that start, however, with a six-inning stint, in which he allowed 2 runs on five hits, and earned his first win as a major leaguer since September 26, 2004, and first as a starter since July 24.

In 2008, Redding went 10-11 with a 4.95 ERA[4] despite his post-All-Star break slump where he went 3-8 with a 6.92 ERA.[5] Redding also was the victim of seven blown saves, tying for first in the majors.[6] At the season's end, he was non-tendered by the Nationals, making him a free agent.[5]

In January 2009, Redding signed a one-year, $2.25 million deal with the New York Mets.[4] Going into spring training, Redding was a candidate to be the fifth starter. He struggled in the games that he pitched in and during the middle of spring training he was "shut down" due to right shoulder fatigue. It was speculated that his shoulder fatigue was caused by his own error. Redding had offseason foot surgery and he had been rushing back to make sure he had secured a spot in the Opening Day rotation.[7] Tim made his first start of the 2009 season on May 18 against the Los Angeles Dodgers and allowed 2 earned runs over 6 innings.[8] He was non-tendered by the Mets following the season.